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61.
Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells
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Johansson C Jonsson M Marttila M Persson D Fan XL Skog J Frängsmyr L Wadell G Arnberg N 《Journal of virology》2007,81(2):954-963
Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells. 相似文献
62.
NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy 总被引:1,自引:1,他引:1
Malmberg KJ Bryceson YT Carlsten M Andersson S Björklund A Björkström NK Baumann BC Fauriat C Alici E Dilber MS Ljunggren HG 《Cancer immunology, immunotherapy : CII》2008,57(10):1541-1552
Insights into the molecular basis for natural killer (NK) cell recognition of human cancer have been obtained in recent years. Here, we review current knowledge on the molecular specificity and function of human NK cells. Evidence for NK cell targeting of human tumors is provided and new strategies for NK cell-based immunotherapy against human cancer are discussed. Based on current knowledge, we foresee a development where more cancers may be subject to treatment with drugs or other immunomodulatory agents affecting NK cells, either directly or indirectly. We also envisage a possibility that certain forms of cancers may be subject to treatment with adoptively transferred NK cells, either alone or in combination with other therapeutic interventions. 相似文献
63.
Clinical guidelines recommend that violence risk be assessed in schizophrenia. Current approaches are resource-intensive as they employ detailed clinical assessments of dangerousness for most patients. An alternative approach would be to first screen out patients at very low risk of future violence prior to more costly and time-consuming assessments. In order to implement such a stepped strategy, we developed a simple tool to screen out individuals with schizophrenia at very low risk of violent offending. We merged high quality Swedish national registers containing information on psychiatric diagnoses, socio-demographic factors, and violent crime. A cohort of 13,806 individuals with hospital discharge diagnoses of schizophrenia was identified and followed for up to 33 years for violent crime. Cox regression was used to determine risk factors for violent crime and construct the screening tool, the predictive validity of which was measured using four outcome statistics. The instrument was calibrated on 6,903 participants and cross-validated using three independent replication samples of 2,301 participants each. Regression analyses resulted in a tool composed of five items: male sex, previous criminal conviction, young age at assessment, comorbid alcohol abuse, and comorbid drug abuse. At 5 years after discharge, the instrument had a negative predictive value of 0.99 (95% CI = 0.98–0.99), meaning that very few individuals who the tool screened out (n = 2,359 out of original sample of 6,903) were subsequently convicted of a violent offence. Screening out patients who are at very low risk of violence prior to more detailed clinical assessment may assist the risk assessment process in schizophrenia. 相似文献
64.
Background
Evidence based and gender specific knowledge about sickness absence following coronary revascularisation is lacking. The objective was to investigate sickness absence after a first coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) among women and men in a national Swedish study.Materials and Methods
All patients 30–63 years of age, who underwent a first CABG (n = 22,985, 16% women) or PCI (40,891, 22% women) in Sweden between 1994 and 2006 were included. Information on sickness absence, co-morbidity, and other patient characteristics was obtained from national registers. Long-term sickness absence (LTSA) was defined as >180 and >90 sick-leave days in the first sick-leave spell following CABG and PCI, respectively. Prevalence ratio (PR) and 95% confidence interval (CI) of LTSA were calculated.Findings
LTSA followed the interventions in 41% and 36% for CABG and PCI patients, respectively. Women had more often LTSA compared with men, (CABG PR = 1.23: 95% CI 1.19–1.28 and PCI PR = 1.19; 95% CI 1.16–1.23). A history of sickness absence the year before the intervention increased the risk for LTSA after the intervention in both genders. Among women, older age, or being self employed or unemployed was associated with a lower risk for LTSA. Among men previous cardiovascular disease, diabetes and low socio-economic position increased the risk. During the observation period, there was no change in sickness absence rates among PCI patients but an increase among CABG patients adjusting for patient characteristics.Conclusion
This national study covering a 13-year period shows that long-term sickness absence following coronary revascularisation is common in Sweden, especially among women, and is associated with socio-economic position, co-morbidity, and sickness absence during the year before the intervention. Gender specific scientific knowledge about use and effects of sickness absence following coronary revascularisation is warranted for the patients, the treating physicians, the healthcare sector, and the society. 相似文献65.
66.
Zhang R Xu Y Ekman N Wu Z Wu J Alitalo K Min W 《The Journal of biological chemistry》2003,278(51):51267-51276
Tumor necrosis factor (TNF), via its receptor 2 (TNFR2), induces Etk (or Bmx) activation and Etk-dependent endothelial cell (EC) migration and tube formation. Because TNF receptor 2 lacks an intrinsic kinase activity, we examined the kinase(s) mediating TNF-induced Etk activation. TNF induces a coordinated phosphorylation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Etk, which is blocked by VEGFR2-specific inhibitors. In response to TNF, Etk and VEGFR2 form a complex resulting in a reciprocal activation between the two kinases. Subsequently, the downstream phosphatidylinositol 3-kinase (PI3K)-Akt signaling (but not signaling through phospholipase C-gamma) was initiated and directly led to TNF-induced EC migration, which was significantly inhibited by VEGFR2-, PI3K-, or Akt-specific inhibitors. Phosphorylation of VEGFR2 at Tyr-801 and Tyr-1175, the critical sites for VEGF-induced PI3K-Akt signaling, was not involved in TNF-mediated Akt activation. However, TNF induces phosphorylation of Etk at Tyr-566, directly mediating the recruitment of the p85 subunit of PI3K. Furthermore, TNF- but not VEGF-induced activation of VEGFR2, Akt, and EC migration are blunted in EC genetically deficient with Etk. Taken together, our data demonstrated that TNF induces transactivation between Etk and VEGFR2, and Etk directly activates PI3K-Akt angiogenic signaling independent of VEGF-induced VEGFR2-PI3K-Akt signaling pathway. 相似文献
67.
Serial peels through the branch junctions of Psilophyton dawsonii were examined in an attempt to determine if “hydraulic constrictions” (i.e., a localized decrease in mean diameter of xylem elements) sensu Zimmermann (1983) had occurred during bifurcation. Based on the mean diameters of primary xylem tracheids measured acropetally and basipetally to branch junctions, evidence for xylem constrictions (= localized decrease in mean tracheid diameter) was found within the basalmost portions of four out of six minor axes examined near their attachment to major axes (anisotomous junctions). Xylem constrictions were not detected in branch junctions between axes of equal girth (isotomous junctions). Xylem constrictions were detected within the base of five out of seven junctions between fertile and main axes. The mean diameters of tracheids of the branch trace near its origin are larger both basipetally and acropetally from the constriction. There is no evidence for a localized decrease in the mean diameter of the xylem strand in the region of a constriction. Therefore, xylem constrictions are not the result of epidogenesis. Based on the production of “hydraulic constrictions” in extant plants, which serve to localize the formation of embolisms in lateral branches during water stress, it is speculated that P. dawsonii could protect the vasculature of major axes by a similar anatomical feature. 相似文献
68.
Ahrman E Gustavsson N Hultschig C Boelens WC Emanuelsson CS 《Extremophiles : life under extreme conditions》2007,11(5):659-666
Citrate synthase (CS) is often used in chaperone assays since this thermosensitive enzyme aggregates at moderately increased
temperatures. Small heat shock proteins (sHsps) are molecular chaperones specialized in preventing the aggregation of other
proteins, termed substrate proteins, under conditions of transient heat stress. To investigate the mechanism whereby sHsps
bind to and stabilize a substrate protein, we here used peptide array screening covering the sequence of porcine CS (P00889).
Strong binding of sHsps was detected to a peptide corresponding to the most N-terminal α-helix in CS (amino acids Leu13 to Gln27). The N-terminal α-helices in the CS dimer intertwine with the C-terminus in the other subunit and together form a stem-like
structure which is protruding from the CS dimer. This stem-like structure is absent in thermostable forms of CS from thermophilic
archaebacteria like Pyrococcus furiosus and Sulfolobus solfatacarium. These data therefore suggest that thermostabilization of thermosensitive CS by sHsps is achieved by stabilization of the
C- and N-terminae in the protruding thermosensitive softspot, which is absent in thermostable forms of the CS dimer. 相似文献
69.
Junpeng Mu Youhong Peng Xinqiang Xi Xinwei Wu Guoyong Li Karl J. Niklas Shucun Sun 《Annals of botany》2015,116(6):899-906
Background and Aims Asymmetric warming is one of the distinguishing features of global climate change, in which winter and night-time temperatures are predicted to increase more than summer and diurnal temperatures. Winter warming weakens vernalization and hence decreases the potential to flower for some perennial herbs, and night warming can reduce carbohydrate concentrations in storage organs. This study therefore hypothesized that asymmetric warming should act to reduce flower number and nectar production per flower in a perennial herb, Saussurea nigrescens, a key nectar plant for pollinators in Tibetan alpine meadows.Methods A long-term (6 years) warming experiment was conducted using open-top chambers placed in a natural meadow and manipulated to achieve asymmetric increases in temperature, as follows: a mean annual increase of 0·7 and 2·7 °C during the growing and non-growing seasons, respectively, combined with an increase of 1·6 and 2·8 °C in the daytime and night-time, respectively, from June to August. Measurements were taken of nectar volume and concentration (sucrose content), and also of leaf non-structural carbohydrate content and plant morphology.Key Results Six years of experimental warming resulted in reductions in nectar volume per floret (64·7 % of control), floret number per capitulum (8·7 %) and capitulum number per plant (32·5 %), whereas nectar concentration remained unchanged. Depletion of leaf non-structural carbohydrates was significantly higher in the warmed than in the ambient condition. Overall plant density was also reduced by warming, which, when combined with reductions in flower development and nectar volumes, led to a reduction of ∼90 % in nectar production per unit area.Conclusions The negative effect of asymmetric warming on nectar yields in S. nigrescens may be explained by a concomitant depletion of leaf non-structural carbohydrates. The results thus highlight a novel aspect of how climate change might affect plant–pollinator interactions and plant reproduction via induction of allocation shifts for plants growing in communities subject to asymmetric warming. 相似文献
70.